Neurocognition and quality of life after reinitiating antiretroviral therapy in children randomized to planned treatment interruption

Objective: Understanding the effects of antiretroviral treatment (ART) interruption on neurocognition and quality of life (QoL) are important for managing unplanned interruptions and planned interruptions in HIV cure research. Design: Children previously randomized to continuous (continuous ART, n=41) vs. planned treatment interruption (PTI, n=47) in the Pediatric European Network for Treatment of AIDS (PENTA) 11 study were enrolled. At study end, PTI children resumed ART. At 1 and 2 years following study end, children were assessed by the coding, symbol search and digit span subtests of Wechsler Intelligence Scale for Children (6-16 years old) or Wechsler Adult Intelligence Scale ( 6517 years old) and by Pediatrics QoL questionnaires for physical and psychological QoL. Transformed scaled scores for neurocognition and mean standardized scores for QoL were compared between arms by t-test and Mann-Whitney U test, respectively. Scores indicating clinical concern were compared (<7 for neurocognition and <70 for QoL tests). Results: Characteristics were similar between arms with a median age of 12.6 years, CD4 + of 830 cells/\u3bcl and HIV RNA of 1.7 log 10 copies/ml. The median cumulative ART exposure was 9.6 in continuous ART vs. 7.7 years in PTI (P=0.02). PTI children had a median of 12 months off ART and had resumed ART for 25.2 months at time of first assessment. Neurocognitive scores were similar between arms for all tests. Physical and psychological QoL scores were no different. About 40% had low neurocognitive and QoL scores indicating clinical concern. Conclusion: No differences in information processing speed, sustained attention, short-term memory and QoL functioning were observed between children previously randomized to continuous ART vs. PTI in the PENTA 11 trial

Venous thromboembolism in immobilized patients with dementia. Findings from the RIETE registry.

BACKGROUND: The natural history of venous thromboembolism (VTE) in patients with dementia has not been thoroughly studied. METHODS: We used the RIETE Registry data to assess the clinical characteristics, treatment strategies and outcome during the first 3 months after acute VTE in all immobilized patients with dementia. RESULTS: As of August 2011, 37988 patients had been enrolled, of whom 1316 (3.5%) had dementia. Most patients in both subgroups were initially treated with low-molecular-weight heparin (LMWH). Then, 48% of patients with dementia and 25% of those without dementia received LMWH as long-term therapy. During the first 3 months of anticoagulant therapy, patients with dementia had a higher incidence of fatal pulmonary embolism (PE): 4.0% vs. 1.2% (odds ratio: 3.3; 95% CI: 2.5-4.4) and fatal bleeding: 1.4% vs. 0.5% (odds ratio: 2.9; 95% CI: 1.8-4.6) than those without dementia. In demented patients initially presenting with PE, the incidence of fatal PE during the first week outweighed that of fatal bleeding (42 vs. 4 deaths), but from Day 8, the incidence of fatal PE was similar to the incidence of fatal bleeding. In patients initially presenting with deep vein thrombosis (DVT), there were 4 fatal PE and 8 fatal bleeding events. CONCLUSIONS: VTE patients with dementia had a high incidence of fatal PE and fatal bleeding. In those initially presenting with PE, the risk of dying of PE far outweighed that of fatal bleeding. In patients presenting with DVT alone, the risk of fatal PE was lower than that of fatal bleeding

Long-term therapy with low-molecular-weight heparin in cancer patients with venous thromboembolism

Long-term therapy with low-molecular-weight heparin (LMWH) is the treatment of choice for cancer patients with venous thromboembolism (VTE). However, the ideal doses of LMWH have not been thoroughly studied. We used the RIETE Registry data to assess the influence of the daily LMWH dosage on outcome during the first three months after VTE. We used propensity score-matching to compare patients who received <150 vs. those receiving 65150 UI/kg/day LMWH. Up to July 2010, 3,222 cancer patients with VTE received long-term therapy with fixed doses of LMWH. Of these, 1,472 (46%) received <150 IU/kg/day (mean, 112 \ub1 28), and 1,750 received 65150 IU/kg/day (mean, 184 \ub1 32). Results of the propensity score matching involved 1269 matched pairs. During follow-up, the incidence of pulmonary embolism (PE) recurrences was similar (1.2% vs. 1.9%), but patients receiving <150 IU/kg/day LMWH had a lower incidence of fatal PE than those treated with 65150 IU/kg/day (0.2% vs. 1.0%; p=0.004). Multivariate analysis confirmed that patients receiving <150 IU/kg/day LMWH had a lower risk for fatal PE (odds ratio [OR]: 0.2; 95% confidence interval [CI]: 0.06-0.8) and for major bleeding (OR: 0.6; 95% CI: 0.3-1.0) than those treated with 65150 IU/kg/day. In real life, one in every two cancer patients with VTE received lower doses of LMWH than those used in randomised trials, with large variations from patient to patient. Unexpectedly, patients treated with <150 IU/kg/day LMWH had fewer fatal PE cases and fewer major bleeding events than those receiving 65150 IU/kg/day LMWH. This finding, however, should be validated in prospective clinical trials

Pulmonary embolism and 3-month outcomes in 4036 patients with venous thromboembolism and chronic obstructive pulmonary disease: data from the RIETE registry

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have a modified clinical presentation of venous thromboembolism (VTE) but also a worse prognosis than non-COPD patients with VTE. As it may induce therapeutic modifications, we evaluated the influence of the initial VTE presentation on the 3-month outcomes in COPD patients. METHODS: COPD patients included in the on-going world-wide RIETE Registry were studied. The rate of pulmonary embolism (PE), major bleeding and death during the first 3 months in COPD patients were compared according to their initial clinical presentation (acute PE or deep vein thrombosis (DVT)). RESULTS: Of the 4036 COPD patients included, 2452 (61%; 95% CI: 59.2-62.3) initially presented with PE. PE as the first VTE recurrence occurred in 116 patients, major bleeding in 101 patients and mortality in 443 patients (Fatal PE: first cause of death). Multivariate analysis confirmed that presenting with PE was associated with higher risk of VTE recurrence as PE (OR, 2.04; 95% CI: 1.11-3.72) and higher risk of fatal PE (OR, 7.77; 95% CI: 2.92-15.7). CONCLUSIONS: COPD patients presenting with PE have an increased risk for PE recurrences and fatal PE compared with those presenting with DVT alone. More efficient therapy is needed in this subtype of patients

Usefulness of Thrombophilia Testing in Venous Thromboembolic Disease: Findings From the RIETE Registry

BACKGROUND: Information on thrombophilia risk factors for patients with upper extremity deep vein thrombosis (UEDVT) is limited. The genetic, acquired, and coagulation risk factors of an acute episode of lower EDVT (LEDVT) or UEDVT, either isolated or associated with pulmonary embolism (PE), were studied. MATERIALS AND METHODS: A total of 4503 patients participated in a thrombophilia study. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated. RESULTS: Mean age of the participants was 55 \ub1 19 years. The risk of LEDVT or UEDVT, isolated or associated with PE, was calculated according to thrombophilia factors. We found association between LEDVT and factor V Leiden ([FVL]; OR: 1.8; 95% CI 1.4-2.4) and resistance to activated protein C ([APC-R]; OR: 1.6; 95% CI 1.1-2.4). The LEDVT + PE presented an association with PTG20210A (OR: 1.5; 95% CI 1.1-2.1). No association was found between the thrombophilic defects studied and UEDVT or UEDVT + PE. CONCLUSIONS: Both FVL and APC-R carriers had the risk of developing LEDVT. The PTG20210A carriers had the risk of developing LEDVT + PE. No thrombophilic defects studied presented risk factors for UEDVT or UEDVT + PE

Thirty-day mortality rate in women with cancer and venous thromboembolism. Findings from the RIETE Registry

The influence of the site of cancer on outcome in cancer women with venous thromboembolism (VTE) is poorly understood. Reliable information on its influence might facilitate better use of prevention strategies. We assessed the 30-day outcome in all women with active cancer in the RIETE Registry, trying to identify if differences exist according to the tumor site. Up to May 2010, 2474 women with cancer and acute VTE had been enrolled. The most common sites were the breast (26%), colon (13%), uterus (9.3%), and haematologic (8.6%) cancers. During the 30-day study period, 329 (13%) patients died. Of them, 71 (2.9%) died of pulmonary embolism (PE), 22 (0.9%) died of bleeding. Fatal PE was more common in women with breast, colorectal, lung or pancreatic cancer (59% of the fatal PEs). Fatal bleeding was more frequent in women with colorectal, haematologic, ovarian cancer or carcinoma of unknown origin (55% of fatal bleedings)

A clinical prognostic model for the identification of low-risk patients with acute symptomatic pulmonary embolism and active cancer.

BACKGROUND: Physicians need a specific risk-stratification tool to facilitate safe and cost-effective approaches to the management of patients with cancer and acute pulmonary embolism (PE). The objective of this study was to develop a simple risk score for predicting 30-day mortality in patients with PE and cancer by using measures readily obtained at the time of PE diagnosis. METHODS: Investigators randomly allocated 1,556 consecutive patients with cancer and acute PE from the international multicenter Registro Informatizado de la Enfermedad TromboEmb\uf3lica to derivation (67%) and internal validation (33%) samples. The external validation cohort for this study consisted of 261 patients with cancer and acute PE. Investigators compared 30-day all-cause mortality and nonfatal adverse medical outcomes across the derivation and two validation samples. RESULTS: In the derivation sample, multivariable analyses produced the risk score, which contained six variables: age > 80 years, heart rate 65 110/min, systolic BP < 100 mm Hg, body weight < 60 kg, recent immobility, and presence of metastases. In the internal validation cohort (n = 508), the 22.2% of patients (113 of 508) classified as low risk by the prognostic model had a 30-day mortality of 4.4% (95% CI, 0.6%-8.2%) compared with 29.9% (95% CI, 25.4%-34.4%) in the high-risk group. In the external validation cohort, the 18% of patients (47 of 261) classified as low risk by the prognostic model had a 30-day mortality of 0%, compared with 19.6% (95% CI, 14.3%-25.0%) in the high-risk group. CONCLUSIONS: The developed clinical prediction rule accurately identifies low-risk patients with cancer and acute PE